SORL1 and SIRT1 mRNA expression and promoter methylation levels in aging and Alzheimer’s Disease

Furuya, Tatiane Katsue; Silva, Patrícia Natália Oliveira da; Payão, Spencer Luíz Marques; Rasmussen, Lucas Trevizani; Lábio, Roger Willian de; Bertolucci, Paulo Henrique Ferreira; Braga, I.; Chen, Elizabeth; Turecki, Gustavo; Mechawar, Naguib; Mill, Jonathan; Smith, Marı́lia de Arruda Cardoso

doi:10.1016/j.neuint.2012.07.014

Cited by 57 publications

(33 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…If this is the case, our findings suggest that the control of Sirt1 protein levels is not exerted through the repression of mRNA expression by promoter hypermethylation. Consistent with the present findings, Furuya et al [39] showed that Sirt1 mRNA levels and promoter methylation in leukocytes did not differ between AD patients and controls. The alignment among ours and Furuya et al's data [39] increases the likelihood that epigenetic modulation by promoter methylation does not play a major role in the peripheral regulation of Sirt1 levels.…”

Section: Discussionsupporting

confidence: 93%

Peripheral leukocyte expression of the potential biomarker proteins Bdnf, Sirt1, and Psen1 is not regulated by promoter methylation in Alzheimer's disease patients

Carboni

Lattanzio

Candeletti

et al. 2015

Neuroscience Letters

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 93%

Peripheral leukocyte expression of the potential biomarker proteins Bdnf, Sirt1, and Psen1 is not regulated by promoter methylation in Alzheimer's disease patients

Carboni

Lattanzio

Candeletti

et al. 2015

Neuroscience Letters

View full text Add to dashboard Cite

“…Higher DUSP22 promoter methylation was found in AD brain tissues [47]. Lower SORL1 promoter methylation was found in the brain and blood of AD patients [48]. Our study showed there was a significantly elevated methylation of the BDNF promoter in peripheral blood.…”

Section: Discussionmentioning

confidence: 45%

Elevation of Peripheral BDNF Promoter Methylation Links to the Risk of Alzheimer's Disease

Chang

Wang

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

Brain derived neurotrophic factor (BDNF) has been known to play an important role in various mental disorders or diseases such as Alzheimer's disease (AD). The aim of our study was to assess whether BDNF promoter methylation in peripheral blood was able to predict the risk of AD. A total of 44 AD patients and 62 age- and gender-matched controls were recruited in the current case-control study. Using the bisulphite pyrosequencing technology, we evaluated four CpG sites in the promoter of the BDNF. Our results showed that BDNF methylation was significantly higher in AD cases than in the controls (CpG1: p = 10.021; CpG2: p = 0.002; CpG3: p = 0.007; CpG4: p = 0.005; average methylation: p = 0.004). In addition, BDNF promoter methylation was shown to be significantly correlated with the levels of alkaline phosphatase (ALP), glucose, Lp(a), ApoE and ApoA in males (ALP: r = −0.308, p = 0.042; glucose: r = −0.383, p = 0.010; Lp(a): r = 0.333, p = 0.027; ApoE: r = −0.345, p = 0.032;), ApoA levels in females (r = 0.362, p = 0.033), and C Reactive Protein (CRP) levels in both genders (males: r = −0.373, p = 0.016; females: r = −0.399, p = 0.021). Our work suggested that peripheral BDNF promoter methylation might be a diagnostic marker of AD risk, although its underlying function remains to be elaborated in the future.

show abstract

“…Alternatively, two studies [50, 51] showed no difference in DNA methylation of APP in brain tissue between AD and healthy controls. Fourteen studies found no difference or clear pattern in methylation of the following genes: 12-LOX [34], debrin-like protein gene [34], p450 epoxygenase gene [34], MAPT , PSEN1 , UCHL1 , SST [52], SSTR4 [52], F2RL2 [45], SOD-1 [48] and GRN [53] in brain tissue; PS1 [49], PS2 [49] and tau1 [49], SMARCA 5 [54], CHD1 [54], BDNF [55], SIRT1 [55], PSEN1 [55{Tannorella, 2015 #2823], genes involved in DNA repair [56], genes involved in homocysteine pathway [57], CTSB [58], CTSD [58], DDT [58], TSC1 [58], NRD1 [58] and NDUFA6 [58] in blood cells; HSPA8 [59], HSPA9 [59], ApoE4 [47, 49], SNAP25 [60], SORL 1 , SIRT1 and SIRT3 [49, 54, 60] in both blood cells and brain tissue (Table 2). However, 7 studies showed differences in methylation patterns of CpG sites (within same gene some CpG sites were hypomethylated and some others were hypermethylated, in AD cases) examined at the following genes: SORL1 [61], ABCA7 [61], SLC2A4 [61], BIN1 [61], HSPA8 [59], HSPA9 [59], DR4 gene [62], BDNF4 [43, 44], SIRT1 [49], APP [47], MAPT [47] and GSK3B [47].…”

Section: Resultsmentioning

confidence: 99%

The Role of DNA Methylation and Histone Modifications in Neurodegenerative Diseases: A Systematic Review

et al. 2016

View full text Add to dashboard Cite

ImportanceEpigenetic modifications of the genome, such as DNA methylation and histone modifications, have been reported to play a role in neurodegenerative diseases (ND) such as Alzheimer’s disease (AD) and Parkinson’s disease (PD).ObjectiveTo systematically review studies investigating epigenetic marks in AD or PD.MethodsEleven bibliographic databases (Embase.com, Medline (Ovid), Web-of-Science, Scopus, PubMed, Cinahl (EBSCOhost), Cochrane Central, ProQuest, Lilacs, Scielo and Google Scholar) were searched until July 11th 2016 to identify relevant articles. We included all randomized controlled trials, cohort, case-control and cross-sectional studies in humans that examined associations between epigenetic marks and ND. Two independent reviewers, with a third reviewer available for disagreements, performed the abstract and full text selection. Data was extracted using a pre-designed data collection form.ResultsOf 6,927 searched references, 73 unique case-control studies met our inclusion criteria. Overall, 11,453 individuals were included in this systematic review (2,640 AD and 2,368 PD outcomes). There was no consistent association between global DNA methylation pattern and any ND. Studies reported epigenetic regulation of 31 genes (including cell communication, apoptosis, and neurogenesis genes in blood and brain tissue) in relation to AD and PD. Methylation at the BDNF, SORBS3 and APP genes in AD were the most consistently reported associations. Methylation of α-synuclein gene (SNCA) was also found to be associated with PD. Seven studies reported histone protein alterations in AD and PD.ConclusionMany studies have investigated epigenetics and ND. Further research should include larger cohort or longitudinal studies, in order to identify clinically significant epigenetic changes. Identifying relevant epigenetic changes could lead to interventional strategies in ND.

show abstract

SORL1 and SIRT1 mRNA expression and promoter methylation levels in aging and Alzheimer’s Disease

Cited by 57 publications

References 8 publications

Peripheral leukocyte expression of the potential biomarker proteins Bdnf, Sirt1, and Psen1 is not regulated by promoter methylation in Alzheimer's disease patients

Peripheral leukocyte expression of the potential biomarker proteins Bdnf, Sirt1, and Psen1 is not regulated by promoter methylation in Alzheimer's disease patients

Elevation of Peripheral BDNF Promoter Methylation Links to the Risk of Alzheimer's Disease

The Role of DNA Methylation and Histone Modifications in Neurodegenerative Diseases: A Systematic Review

Contact Info

Product

Resources

About